公开(公告)号：US08008488B2

公开(公告)日：2011-08-30

申请号：US10548931

申请日：2004-03-12

申请人： Hervé Geneste ,  Andreas Kling ,  Wilfried Braje ,  Andreas Haupt ,  Liliane Unger

发明人： Hervé Geneste ,  Andreas Kling ,  Wilfried Braje ,  Andreas Haupt ,  Liliane Unger

IPC分类号： C07D403/06 ,  C07D403/14 ,  C07D401/06 ,  C07D401/14 ,  A61K31/505 ,  A61K31/506 ,  A61P25/16 ,  A61P25/18 ,  A61P25/24 ,  A61P25/22 ,  A61P25/30

CPC分类号： C07D239/36 ,  C07D239/52 ,  C07D239/54 ,  C07D239/553 ,  C07D239/56 ,  C07D401/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14

摘要： The invention relates to pyrimidin 2-one compounds of general formula (I), in addition to the derivatives and tautomers of (I) and the physiologically acceptable salts of said compounds. In said formula, A represents linear or branched C3-C6 alkene, which can have a double bond or triple bond and/or a group Z, which is not adjacent to the nitrogen atom of the pyrimidinone ring and is selected from O, S, C(O), NR3, C(O)NR3, NR3C(O), OC(O) and C(O)O; B represents a group of the formula (II), in which X stands for CH2 or N and Y stands for CH2 or CH2CH2, or X—Y can also jointly represent C═CH, C═CH—CH2 or CH—CH═CH; R1 and R2 are defined as cited in the description and the claims; and Ar represents an optionally substituted aromatic group. The invention also relates to a pharmaceutical agent, containing at least one compound (I) and the tautomers, derivatives and/or acid addition salts of said compound, optionally together with physiologically acceptable carriers and/or auxiliary agents. The invention also relates to the use of compounds of formula (I), and their tautomers, derivatives and pharmacologically acceptable acid addition salts for producing a pharmaceutical agent for treating diseases which respond to the influence of dopamine D3 receptor ligands.

摘要翻译： 除了（I）的衍生物和互变异构体以及所述化合物的生理学上可接受的盐之外，本发明涉及通式（I）的嘧啶-2-酮化合物。 在所述式中，A表示可以具有双键或三键的直链或支链C 3 -C 6烯基和/或不与嘧啶酮环的氮原子相邻并且选自O，S， C（O），NR 3，C（O）NR 3，NR 3 C（O），OC（O）和C（O）O; B表示式（II）的基团，其中X表示CH2或N，Y表示CH2或CH2CH2，或X-Y也可共同表示C = CH，C = CH-CH 2或CH-CH = CH ; R1和R2定义为在说明书和权利要求书中引用的; 并且Ar表示任选取代的芳族基团。 本发明还涉及含有至少一种化合物（I）和所述化合物的互变异构体，衍生物和/或酸加成盐，任选地与生理上可接受的载体和/或辅助剂一起的药剂。 本发明还涉及式（I）化合物及其互变异构体，衍生物和药理学上可接受的酸加成盐的用途，用于制备用于治疗对多巴胺D3受体配体的影响作出反应的疾病的药剂。

公开(公告)号：US08492540B2

公开(公告)日：2013-07-23

申请号：US12740714

申请日：2008-10-31

申请人： Wilfried Braje ,  Sean Colm Turner ,  Andreas Haupt ,  Udo Lange ,  Hervé Geneste ,  Karla Drescher ,  Liliane Unger ,  Ana Lucia Relo ,  Anton Bespalov

发明人： Wilfried Braje ,  Sean Colm Turner ,  Andreas Haupt ,  Udo Lange ,  Hervé Geneste ,  Karla Drescher ,  Liliane Unger ,  Ana Lucia Relo ,  Anton Bespalov

IPC分类号： C07D253/075 ,  C07D403/14 ,  A61K31/53 ,  A61P25/18 ,  A61P25/30 ,  A61P25/00

CPC分类号： C07D403/12

摘要： The invention relates to compounds of the formula I: wherein A is a saturated or unsaturated hydrocarbon chain having a chain length of 4 to 6 carbon atoms, the hydrocarbon chain being unsubstituted or substituted by 1, 2 or 3 methyl groups; R1 is selected from the group consisting of hydrogen, C1-C3 alkyl and fluorinated C1-C3 alkyl; R2 is hydrogen, halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, fluorinated C1-C3 alkyl or fluorinated C1-C3 alkoxy; R3 is selected from the group consisting of branched C4-C6 alkyl and C3-C6 cycloalkyl, and R4 is C1-C6 alkyl, C3-C6 cycloalkyl, fluorinated C1-C3-alkyl and fluorinated C3-C6 cycloalkyl. and the physiologically tolerated salts of these compounds and the N-oxides thereof. The invention also relates to a pharmaceutical composition that comprises at least one compound of the formula I and/or at least one physiologically tolerated acid addition salt thereof, and further to a method for treating disorders that respond beneficially to dopamine D3 receptor antagonists or dopamine D3 agonists, said method comprising administering an effective amount of at least one compound or physiologically tolerated acid addition salt of the formula I to a subject in need thereof.

摘要翻译： 本发明涉及式I化合物：其中A是链长为4-6个碳原子的饱和或不饱和烃链，烃链未被取代或被1,2或3个甲基取代; R1选自氢，C1-C3烷基和氟化C1-C3烷基; R2是氢，卤素，氰基，C1-C3烷基，C1-C3烷氧基，氟化C1-C3烷基或氟化C1-C3烷氧基; R3选自支链C4-C6烷基和C3-C6环烷基，R4为C1-C6烷基，C3-C6环烷基，氟化C1-C3-烷基和氟化C3-C6环烷基。 以及这些化合物的生理上耐受的盐及其N-氧化物。 本发明还涉及包含至少一种式I化合物和/或其至少一种生理上耐受的酸加成盐的药物组合物，还涉及治疗有益于多巴胺D3受体拮抗剂或多巴胺D3的病症的方法 所述方法包括向有需要的受试者施用有效量的至少一种式I化合物或生理学上耐受的酸加成盐。

公开(公告)号：US20110245266A1

公开(公告)日：2011-10-06

申请号：US13103734

申请日：2011-05-09

申请人： Hervé Geneste ,  Wilfried Braje ,  Andreas Haupt

发明人： Hervé Geneste ,  Wilfried Braje ,  Andreas Haupt

IPC分类号： A61K31/497 ,  C07D403/14 ,  A61P25/18 ,  A61P25/24

CPC分类号： C07D401/12

摘要： The invention relates to novel pyridin-2-one compounds of general formula (I), in which A represents a 4- to 6-membered hydrocarbon chain that can have 1 or 2 methyl groups as substituents, wherein 1 or 2 carbon atoms can be replaced by oxygen, a carbonyl group or sulfur, and the hydrocarbon chain can have a double bond or a triple bond; R1, R2, R3 and R4 have the meanings as cited in the claims and in the description. The invention also relates to the tautomers of compounds I, the physiologically acceptable salts of compounds I, and to the physiologically acceptable salts of the tautomers of compounds I. The invention also relates to the use of compounds of general formula (I) and of the tautomers, and to the use of the physiologically acceptable salts of compounds I and of the tautomers for producing a pharmaceutical agent for treating diseases that respond to the influence of dopamine D3 receptor antagonists or agonists.

摘要翻译： 本发明涉及通式（I）的新型吡啶-2-酮化合物，其中A表示可具有1或2个甲基作为取代基的4至6元烃链，其中1或2个碳原子可以是 由氧，羰基或硫取代，烃链可以具有双键或三键; R1，R2，R3和R4具有权利要求书和说明书中引用的含义。 本发明还涉及化合物I的互变异构体，化合物I的生理上可接受的盐，以及化合物I的互变异构体的生理上可接受的盐。本发明还涉及通式（I）的化合物和 互变异构体，以及化合物I和互变异构体的生理上可接受的盐的用途，用于制备用于治疗对多巴胺D3受体拮抗剂或激动剂的影响作出反应的疾病的药剂。

公开(公告)号：US08334289B2

公开(公告)日：2012-12-18

申请号：US13103734

申请日：2011-05-09

申请人： Hervé Geneste ,  Wilfried Braje ,  Andreas Haupt

发明人： Hervé Geneste ,  Wilfried Braje ,  Andreas Haupt

IPC分类号： A61K31/506

CPC分类号： C07D401/12

摘要： The invention relates to novel pyridin-2-one compounds of general formula (I), in which A represents a 4- to 6-membered hydrocarbon chain that can have 1 or 2 methyl groups as substituents, wherein 1 or 2 carbon atoms can be replaced by oxygen, a carbonyl group or sulfur, and the hydrocarbon chain can have a double bond or a triple bond; R1, R2, R3 and R4 have the meanings as cited in the claims and in the description. The invention also relates to the tautomers of compounds I, the physiologically acceptable salts of compounds I, and to the physiologically acceptable salts of the tautomers of compounds I. The invention also relates to the use of compounds of general formula (I) and of the tautomers, and to the use of the physiologically acceptable salts of compounds I and of the tautomers for producing a pharmaceutical agent for treating diseases that respond to the influence of dopamine D3 receptor antagonists or agonists.

摘要翻译： 本发明涉及通式（I）的新型吡啶-2-酮化合物，其中A表示可具有1或2个甲基作为取代基的4至6元烃链，其中1或2个碳原子可以是 由氧，羰基或硫取代，烃链可以具有双键或三键; R1，R2，R3和R4具有权利要求书和说明书中引用的含义。 本发明还涉及化合物I的互变异构体，化合物I的生理上可接受的盐，以及化合物I的互变异构体的生理上可接受的盐。本发明还涉及通式（I）的化合物和 互变异构体，以及化合物I和互变异构体的生理上可接受的盐的用途，用于制备用于治疗对多巴胺D3受体拮抗剂或激动剂的影响作出反应的疾病的药剂。

公开(公告)号：US06919342B2

公开(公告)日：2005-07-19

申请号：US10860823

申请日：2004-06-04

申请人： Andreas Haupt ,  Roland Grandel ,  Wilfried Braje ,  Hervé Geneste ,  Karla Drescher ,  Dorothea Starck ,  Hans-Jürgen Teschendorf

发明人： Andreas Haupt ,  Roland Grandel ,  Wilfried Braje ,  Hervé Geneste ,  Karla Drescher ,  Dorothea Starck ,  Hans-Jürgen Teschendorf

IPC分类号： A61K31/506 ,  C07D403/12 ,  C07D403/14

CPC分类号： C07D403/12

摘要： The invention relates to triazole compounds of the general formula I wherein R1 is hydrogen or methyl, and R2 is C3-C4 alkyl or C1-C2 fluoroalkyl, as well as the physiologically tolerated acid addition salts of these compounds. The invention also relates to a pharmaceutical composition that comprises at least one triazole compound of the formula I and/or at least one physiologically tolerated acid addition salt thereof, and further to a method for treating disorders that respond beneficially to dopamine D3 receptor antagonists or dopamine D3 agonists, said method comprising administering an effective amount of at least one triazole compound or physiologically tolerated acid addition salt of the formula I to a subject in need thereof.

摘要翻译： 本发明涉及通式Ⅰ的三唑化合物，其中R 1是氢或甲基，R 2是C 3 -C 3 > 4个烷基或C 1 -C 2 - 氟代烷基，以及这些化合物的生理上耐受的酸加成盐。 本发明还涉及一种药物组合物，其包含至少一种式I的三唑化合物和/或其至少一种生理上耐受的酸加成盐，还涉及治疗有益于多巴胺D 3的病症的方法 受体拮抗剂或多巴胺D 3激动剂，所述方法包括向有需要的受试者施用有效量的至少一种式III的三唑化合物或生理耐受的酸加成盐。

公开(公告)号：US07320979B2

公开(公告)日：2008-01-22

申请号：US10823317

申请日：2004-04-13

申请人： Wilfried M. Braje ,  Andreas Haupt ,  Wilfried Lubisch ,  Roland Grandel ,  Karla Drescher ,  Hervé Geneste ,  Liliane Unger ,  Daryl R. Sauer ,  Sean C. Turner

发明人： Wilfried M. Braje ,  Andreas Haupt ,  Wilfried Lubisch ,  Roland Grandel ,  Karla Drescher ,  Hervé Geneste ,  Liliane Unger ,  Daryl R. Sauer ,  Sean C. Turner

IPC分类号： A61K31/496 ,  A61K31/506 ,  C07D213/72 ,  C07D213/74 ,  C07D239/48

CPC分类号： C07D213/76 ,  C07D213/74 ,  C07D239/69 ,  C07D401/04 ,  C07D487/08

摘要： The invention relates to N-[(piperazinyl)hetaryl]arylsulfonamide compounds of the general formula I in which Q is a bivalent, 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents Ra which is/are selected, independently of each other, from halogen, CN, NO2, CO2R4, COR5, C1-C4-alkyl and C1-C4-haloalkyl; Ar is phenyl or a 6-membered heteroaromatic radical which possesses 1 or 2 N atoms as ring members and which optionally carries one or two substituents Rb, which is/are selected from halogen, NO2, CN, CO2R4, COR5, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl and C1-C4-haloalkyl, with it also being possible for two radicals Rb which are bonded to adjacent C atoms of Ar to be together C3-C4-alkylene; R1 is hydrogen, C1-C4-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C4-alkenyl or C3-C4-alkynyl; with the radicals n, R1, R2, R3, R4 and R5 having the meanings given in the patent claims, to the N-oxides and to the physiologically tolerated acid addition salts of these compounds and to pharmaceutical compositions which comprise at least one N-[(piperazinyl)hetaryl]arylsulfonamide compound as claimed in one of claims 1 to 10 and/or at least one physiologically tolerated acid addition salt of I and/or an N-oxide of I, where appropriate together with physiologically acceptable carriers and/or auxiliary substances for treating diseases which respond to influencing by dopamine D3 receptor antagonists or agonists, in particular for treating diseases of the central nervous system and disturbances of kidney function.

公开(公告)号：US07465744B2

公开(公告)日：2008-12-16

申请号：US10544550

申请日：2004-02-05

申请人： Dorothea Starck ,  Hans-Jörg Treiber ,  Thomas Zierke ,  Georg Kettschau ,  Hervé Geneste ,  Andreas Haupt ,  Liliane Unger ,  Kai Blumbach ,  Dietmar Schöbel ,  Hans-Jurgen Teschendorf

发明人： Dorothea Starck ,  Hans-Jörg Treiber ,  Thomas Zierke ,  Georg Kettschau ,  Hervé Geneste ,  Andreas Haupt ,  Liliane Unger ,  Kai Blumbach ,  Dietmar Schöbel ,  Hans-Jurgen Teschendorf

IPC分类号： A61K31/41 ,  C07D401/02

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14

摘要： The invention relates to triazole compounds of general formula (I), wherein A, B, R1, R2, R3 and R4 have the meaning cited in claim 1. The invention also relates to a pharmaceutical agent containing at least one compound of general formula (I) in addition to the use of the compound (I) for producing a pharmaceutical agent for treating illnesses, responding to the effects of dopamine-D3-receptor antagonists or dopamine-D3-receptor agonists, especially for treating disorders in the central nervous system.

摘要翻译： 本发明涉及通式（I）的三唑化合物，其中A，B，R 1，R 2，R 3和R 4具有权利要求1中引用的含义。本发明还涉及含有至少一种通式（ I），除了使用化合物（I）制备用于治疗疾病的药剂之外，还应对多巴胺-D3受体拮抗剂或多巴胺-D 3受体激动剂的作用，特别是用于治疗中枢神经系统疾病 。

公开(公告)号：US08969552B2

公开(公告)日：2015-03-03

申请号：US11665428

申请日：2005-10-14

申请人： Karla Drescher ,  Andreas Haupt ,  Liliane Unger ,  Sean C. Turner ,  Wilfried Braje ,  Roland Grandel ,  Christophe Henry

发明人： Karla Drescher ,  Andreas Haupt ,  Liliane Unger ,  Sean C. Turner ,  Wilfried Braje ,  Roland Grandel ,  Christophe Henry

IPC分类号： C07C311/44 ,  C07D207/10 ,  C07D211/10 ,  C07D215/38 ,  C07D263/32 ,  C07D413/04 ,  C07C311/21 ,  C07C311/29 ,  C07D239/84 ,  C07D277/82 ,  C07D311/04 ,  C07D491/04

CPC分类号： C07C311/21 ,  C07C311/29 ,  C07C311/44 ,  C07C2601/02 ,  C07C2602/10 ,  C07D207/10 ,  C07D211/10 ,  C07D215/38 ,  C07D239/84 ,  C07D263/32 ,  C07D277/82 ,  C07D311/04 ,  C07D413/04 ,  C07D491/04

摘要： The present invention relates to aromatic compounds of the formula I wherein Ar is phenyl or an aromatic 5- or 6-membered C-bound heteroaromatic radical, wherein Ar may carry 1 radical Ra and wherein Ar may also carry 1 or 2 radicals Rb; X is N or CH; Y is O, S, —CH═N—, —CH═CH— or —N═CH—; A is CH2, O or S; E is CR6R7 or NR3; R1 is C1-C4-alkyl, C3-C4-cycloalkyl, C3-C4-cycloalkylmethyl, C3-C4-alkenyl, fluorinated C1-C4-alkyl, fluorinated C3-C4-cycloalkyl, fluorinated C3-C4-cycloalkylmethyl, fluorinated C3-C4-alkenyl, formyl or C1-C3-alkylcarbonyl; R1a is H, C2-C4-alkyl, C3-C4-cycloalkyl, C3-C4-alkenyl, fluorinated C1-C4-alkyl, fluorinated C3-C4-cycloalkyl, or R1a and R2 together are (CH2)n with n being 2 or 3, or R1a and R2a together are (CH2)n with n being 2 or 3; R2 and R2a are independently of each other H, CH3, CH2F, CHF2 or CF3; R3 is H or C1-C4-alkyl; R6, R7 independently of each other are selected from H, C1-C2-alkyl and fluorinated C1-C2-alkyl; and the physiologically tolerated acid addition salts thereof. The invention also relates to the use of a compound of the formula I or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment of a medical disorder susceptible to treatment with a dopamine D3 receptor ligand.

摘要翻译： 本发明涉及式I的芳族化合物，其中Ar是苯基或芳族5-或6-元C-结合的杂芳族基团，其中Ar可以带有1个基团R a，并且其中Ar也可以带有1个或2个基团Rb; X为N或CH; Y是O，S，-CH = N - ， - CH = CH-或-N = CH-; A是CH 2，O或S; E为CR6R7或NR3; R 1是C 1 -C 4烷基，C 3 -C 4环烷基，C 3 -C 4环烷基甲基，C 3 -C 4链烯基，氟化C 1 -C 4烷基，氟化C 3 -C 4环烷基，氟化C 3 -C 4环烷基甲基， C4-烯基，甲酰基或C1-C3-烷基羰基; R1a为H，C2-C4-烷基，C3-C4-环烷基，C3-C4-烯基，氟化C1-C4-烷基，氟化C3-C4-环烷基或R1a和R2一起为（CH2）n，n为2 或3，或R 1a和R 2a一起为（CH 2）n，其中n为2或3; R2和R2a彼此独立地为H，CH3，CH2F，CHF2或CF3; R3是H或C1-C4-烷基; R6，R7彼此独立地选自H，C1-C2-烷基和氟化C1-C2-烷基; 及其生理上耐受的酸加成盐。 本发明还涉及式I化合物或其药学上可接受的盐在制备用于治疗易受多巴胺D3受体配体治疗的医学疾病的药物组合物中的用途。

公开(公告)号：US08207160B2

公开(公告)日：2012-06-26

申请号：US10583590

申请日：2004-12-17

申请人： Wilfried Braje ,  Andreas Haupt ,  Wilfried Lubisch ,  Roland Grandel ,  Karla Drescher ,  Herve Geneste ,  Liliane Unger ,  Daryl R. Sauer

发明人： Wilfried Braje ,  Andreas Haupt ,  Wilfried Lubisch ,  Roland Grandel ,  Karla Drescher ,  Herve Geneste ,  Liliane Unger ,  Daryl R. Sauer

IPC分类号： A61P25/00 ,  A61K31/55 ,  C07D223/16 ,  C07D409/12

CPC分类号： C07D223/16 ,  C07D409/12

摘要： The invention relates to tetrahydrobenzazepines of the general formula I in which the variables Ar, A, B, Y, R1 and R2 have the meanings indicated in claim 1, as well as the N-oxides of these compounds, the physiologically tolerated acid addition salts of these compounds and the physiologically tolerated acid addition salts of the N-oxides. The invention also relates to a pharmaceutical composition that comprises at least one tetrahydrobenzazepine compound of the formula I, the physically tolerated acid addition salt of I, the N-oxide of compound of the formula I and/or the physically tolerated acid addition salts of the N-oxides of I, and further to the use of a compound according to the present invention for treating disorders that respond beneficially to dopamine D3 receptor antagonists or dopamine D3 agonists. The compounds according to the invention are preferably useful for the treatment of disorders of the central nervous system such as schizophrenia and depression and for the treatment of renal function disorders.

摘要翻译： 本发明涉及通式Ⅰ的四氢苯并吖庚因，其中变量Ar，A，B，Y，R 1和R 2具有权利要求1所示的含义，以及这些化合物的N-氧化物，生理上耐受的酸加成盐 的这些化合物和N-氧化物的生理上耐受的酸加成盐。 本发明还涉及药物组合物，其包含至少一种式I的四氢苯并氮杂化合物，I的物理耐受的酸加成盐，式I化合物的N-氧化物和/或其物理上耐受的酸加成盐 I的N-氧化物，并且进一步使用根据本发明的化合物用于治疗有益于多巴胺D3受体拮抗剂或多巴胺D3激动剂的病症。 根据本发明的化合物优选可用于治疗中枢神经系统疾病如精神分裂症和抑郁症以及治疗肾功能障碍。

公开(公告)号：US08486984B2

公开(公告)日：2013-07-16

申请号：US11665287

申请日：2005-10-14

申请人： Karla Drescher ,  Andreas Haupt ,  Liliane Unger ,  Sean C. Turner ,  Wilfried Braje ,  Roland Grandel

发明人： Karla Drescher ,  Andreas Haupt ,  Liliane Unger ,  Sean C. Turner ,  Wilfried Braje ,  Roland Grandel

IPC分类号： A61K31/404 ,  A61K31/4184 ,  C07D209/14 ,  C07D235/14

CPC分类号： C07D471/04 ,  C07D209/14 ,  C07D209/62 ,  C07D235/14

摘要： The present invention relates to an aminomethyl substituted bicyclic aromatic compound of the formula I The invention also relates to the use of a compound of the formula I or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment of a medical disorder susceptible to treatment with a dopamine D3 receptor ligand.

摘要翻译： 本发明涉及式I的氨基甲基取代的双环芳族化合物。本发明还涉及式I化合物或其药学上可接受的盐在制备用于治疗易受治疗的医学疾病的药物组合物中的用途 与多巴胺D3受体配体。